Macrophages and their interactions with oncolytic viruses

• Macrophages have diverse functions and exhibit high functional plasticity.
• Tumour-associated macrophages (TAMs) often assist tumour growth.
• Oncolytic viruses combine targeted toxicity and expression of therapeutic biologics.
• ‘Arming’ oncolytic viruses to modify TAM function provides a new approach for cancer therapy.

Macrophages are a highly plastic cell type and exhibit a range of defensive and regulatory functions in normal physiology. Phagocytic macrophages play an important role in defending against virus infection and they provide an important barrier that can limit the delivery of therapeutic viruses from the injection to the tumour. Within tumours, macrophages generally adopt an immunosuppressive phenotype and are associated with poor clinical prognosis. However their plasticity also provides the opportunity for therapeutic ‘re-education’ of tumour-associated macrophages (TAMs) to adopt an active anticancer role. Oncolytic viruses present the possibility for non-specific stimulation of TAMs, and also the option for tumour-targeted expression of cytokines chosen specifically to modulate macrophage activation.